A comparative study of the Au-catalyzed cyclization of hydroxy-substituted allylic alcohols and ethers

The Au(I)-catalyzed cyclization of hydroxyallylic ethers to form tetrahydropyrans is reported. Employing (acetonitrile)[(o-biphenyl)di-tert-butylphosphine]gold(I) hexafluoroantimonate, the cyclization reactions were complete within minutes to hours, depending on the substrate. The reaction progress was monitored by GC, and comparisons between substrates demonstrate that reactions of allylic alcohols are faster than the corresponding ethers. Additionally, it is reported that Reaxa QuadraPureTM MPA is an efficient scavenging reagent that halts the reaction progress

Multiple Mechanisms in Pd(II)-Catalyzed S_N2′ Reactions of Allylic Alcohols

Density functional calculations and experiments were used to examine mechanisms of Pd­(II) catalyzed intramolecular cyclization and dehydration in acyclic and bicyclic monoallylic diols, a formal SN2′ reaction. In contrast to the previously proposed syn-oxypalladation mechanism for acyclic monoallylic diols, calculations and experiments strongly suggest that hydrogen bonding templates a hydroxyl group and Pd addition across the alkene and provides a low energy pathway via anti-addition (anti-oxypalladation) followed by intramolecular proton transfer and anti-elimination of water. This anti-addition, anti-elimination pathway also provides a simple rationale for the observed stereospecificity. For bicyclic monoallylic diol compounds, Pd­(II) is capable of promoting either anti- or syn-addition. In addition, palladium chloride ligands can mediate proton transfer to promote dehydration when direct intramolecular proton transfer between diol groups is impossible

The Importance of Hydrogen Bonding to Stereoselectivity and Catalyst Turnover in Gold-Catalyzed Cyclization of Monoallylic Diols

Density functional calculations and experiment were used to examine the mechanism, reactivity, and origin of chirality transfer in monophosphine Au-catalyzed monoallylic diol cyclization reactions. The lowest energy pathway for cyclization involves a two-step sequence that begins with intramolecular C–O bond formation by <i>anti</i>-addition of the non-allylic hydroxyl group to the Au-coordinated alkene followed by concerted hydrogen transfer/<i>anti</i>-elimination to liberate water. Concerted S_N2′-type transition states were found to be significantly higher in energy. The two-step cyclization pathway is extremely facile due to hydrogen bonding between diol groups that induces nucleophilic attack on the alkene and then proton transfer between diol groups after C–O bond formation. Importantly, intramolecular proton transfer and elimination provides an extremely efficient avenue for catalyst regeneration from the Au–C σ-bond intermediate, in contrast to other Au-catalyzed cyclization reactions where this intermediate severely restricts catalyst turnover. The origin of chirality transfer and the ensuing alkene stereochemistry is also the result of strong hydrogen-bonding interactions between diol groups. In the C–O bond-forming step, requisite hydrogen bonding biases the tethered nucleophilic moiety to adopt a chair-like conformation with substituents in either axial or equatorial positions, dictating the stereochemical outcome of the reaction. Since this hydrogen bonding is maintained throughout the course of the reaction, establishment of the resultant olefin geometry is also attributed to this templating effect. These computational conclusions are supported by experimental evidence employing bicyclic systems to probe the facial selectivity